Constantinos Zambirinis

Constantinos Zambirinis

Constantinos Zambirinis, MD, MRes

Profile:

My previous research has focused on tumor immunology and the interplay between immune cells and other components of the tumor stroma in promoting of pancreatic carcinogenesis. I am currently expanding on that work by investigating the changes occuring in distant organs prior to the occurence of metastasis. In particular, I’m studying how tumor-derived soluble factors can influence the liver to generate “pre-metastatic niches” that support engraftment of circulating tumor cells. Working together with other members of our group, we aim to devise novel ways to detect these processes early on, in order to predict which patients will develop metastasis in certain organs, and treat them accordingly.


Funding Info:

MSKCC Center for Metastasis Research Fellowship (11/2016-10/2018).


Publications:

  1. Wach, MM, van Beek, E, Ayabe, R, Ruff, S, Brown, Z, Goldman, DA et al.. Metastatic squamous cell carcinoma of known and unknown primary origin treated with axillary or inguinal lymphadenectomy. Am. J. Surg. 2018;216 (5):963-968. doi: 10.1016/j.amjsurg.2018.06.006. PubMed PMID:30143231 .
  2. Pushalkar, S, Hundeyin, M, Daley, D, Zambirinis, CP, Kurz, E, Mishra, A et al.. The Pancreatic Cancer Microbiome Promotes Oncogenesis by Induction of Innate and Adaptive Immune Suppression. Cancer Discov. 2018;8 (4):403-416. doi: 10.1158/2159-8290.CD-17-1134. PubMed PMID:29567829 PubMed Central PMC6225783.
  3. Zheng, J, Hernandez, JM, Doussot, A, Bojmar, L, Zambirinis, CP, Costa-Silva, B et al.. Extracellular matrix proteins and carcinoembryonic antigen-related cell adhesion molecules characterize pancreatic duct fluid exosomes in patients with pancreatic cancer. HPB (Oxford). 2018;20 (7):597-604. doi: 10.1016/j.hpb.2017.12.010. PubMed PMID:29339034 .
  4. Zambirinis, CP, Miller, G. Cancer Manipulation of Host Physiology: Lessons from Pancreatic Cancer. Trends Mol Med. 2017;23 (5):465-481. doi: 10.1016/j.molmed.2017.03.003. PubMed PMID:28400243 PubMed Central PMC5480288.
  5. Daley, D, Mani, VR, Mohan, N, Akkad, N, Ochi, A, Heindel, DW et al.. Dectin 1 activation on macrophages by galectin 9 promotes pancreatic carcinoma and peritumoral immune tolerance. Nat. Med. 2017;23 (5):556-567. doi: 10.1038/nm.4314. PubMed PMID:28394331 PubMed Central PMC5419876.
  6. Daley, D, Zambirinis, CP, Seifert, L, Akkad, N, Mohan, N, Werba, G et al.. γδ T Cells Support Pancreatic Oncogenesis by Restraining αβ T Cell Activation. Cell. 2016;166 (6):1485-1499.e15. doi: 10.1016/j.cell.2016.07.046. PubMed PMID:27569912 PubMed Central PMC5017923.
  7. Seifert, L, Werba, G, Tiwari, S, Giao Ly, NN, Alothman, S, Alqunaibit, D et al.. The necrosome promotes pancreatic oncogenesis via CXCL1 and Mincle-induced immune suppression. Nature. 2016;532 (7598):245-9. doi: 10.1038/nature17403. PubMed PMID:27049944 PubMed Central PMC4833566.
  8. Seifert, L, Deutsch, M, Alothman, S, Alqunaibit, D, Werba, G, Pansari, M et al.. Dectin-1 Regulates Hepatic Fibrosis and Hepatocarcinogenesis by Suppressing TLR4 Signaling Pathways. Cell Rep. 2015;13 (9):1909-1921. doi: 10.1016/j.celrep.2015.10.058. PubMed PMID:26655905 PubMed Central PMC4681001.
  9. Zambirinis, CP, Levie, E, Nguy, S, Avanzi, A, Barilla, R, Xu, Y et al.. TLR9 ligation in pancreatic stellate cells promotes tumorigenesis. J. Exp. Med. 2015;212 (12):2077-94. doi: 10.1084/jem.20142162. PubMed PMID:26481685 PubMed Central PMC4647258.
  10. Greco, SH, Tomkötter, L, Vahle, AK, Rokosh, R, Avanzi, A, Mahmood, SK et al.. TGF-β Blockade Reduces Mortality and Metabolic Changes in a Validated Murine Model of Pancreatic Cancer Cachexia. PLoS ONE. 2015;10 (7):e0132786. doi: 10.1371/journal.pone.0132786. PubMed PMID:26172047 PubMed Central PMC4501823.
  11. Deutsch, M, Graffeo, CS, Rokosh, R, Pansari, M, Ochi, A, Levie, EM et al.. Divergent effects of RIP1 or RIP3 blockade in murine models of acute liver injury. Cell Death Dis. 2015;6 :e1759. doi: 10.1038/cddis.2015.126. PubMed PMID:25950489 PubMed Central PMC4669705.
  12. Parente-Pereira, AC, Shmeeda, H, Whilding, LM, Zambirinis, CP, Foster, J, van der Stegen, SJ et al.. Adoptive immunotherapy of epithelial ovarian cancer with Vγ9Vδ2 T cells, potentiated by liposomal alendronic acid. J. Immunol. 2014;193 (11):5557-66. doi: 10.4049/jimmunol.1402200. PubMed PMID:25339667 .
  13. Zambirinis, CP, Pushalkar, S, Saxena, D, Miller, G. Pancreatic cancer, inflammation, and microbiome. Cancer J. ;20 (3):195-202. doi: 10.1097/PPO.0000000000000045. PubMed PMID:24855007 PubMed Central PMC4112373.
  14. Rao, R, Graffeo, CS, Gulati, R, Jamal, M, Narayan, S, Zambirinis, CP et al.. Interleukin 17-producing γδT cells promote hepatic regeneration in mice. Gastroenterology. 2014;147 (2):473-84.e2. doi: 10.1053/j.gastro.2014.04.042. PubMed PMID:24801349 PubMed Central PMC4123443.
  15. Zambirinis, CP, Ochi, A, Barilla, R, Greco, S, Deutsch, M, Miller, G et al.. Induction of TRIF- or MYD88-dependent pathways perturbs cell cycle regulation in pancreatic cancer. Cell Cycle. 2013;12 (8):1153-4. doi: 10.4161/cc.24488. PubMed PMID:23549168 PubMed Central PMC3674074.
  16. Rehman, A, Hemmert, KC, Ochi, A, Jamal, M, Henning, JR, Barilla, R et al.. Role of fatty-acid synthesis in dendritic cell generation and function. J. Immunol. 2013;190 (9):4640-9. doi: 10.4049/jimmunol.1202312. PubMed PMID:23536633 PubMed Central PMC3633656.
  17. Zambirinis, CP, Miller, G. Signaling via MYD88 in the pancreatic tumor microenvironment: A double-edged sword. Oncoimmunology. 2013;2 (1):e22567. doi: 10.4161/onci.22567. PubMed PMID:23483804 PubMed Central PMC3583926.
  18. Henning, JR, Graffeo, CS, Rehman, A, Fallon, NC, Zambirinis, CP, Ochi, A et al.. Dendritic cells limit fibroinflammatory injury in nonalcoholic steatohepatitis in mice. Hepatology. 2013;58 (2):589-602. doi: 10.1002/hep.26267. PubMed PMID:23322710 PubMed Central PMC3638069.
  19. Kontogianni, P, Zambirinis, CP, Theodoropoulos, G, Gazouli, M, Michalopoulos, NV, Flessas, J et al.. The impact of the stromal cell-derived factor-1-3'A and E-selectin S128R polymorphisms on breast cancer. Mol. Biol. Rep. 2013;40 (1):43-50. doi: 10.1007/s11033-012-1989-x. PubMed PMID:23129313 .
  20. Ochi, A, Graffeo, CS, Zambirinis, CP, Rehman, A, Hackman, M, Fallon, N et al.. Toll-like receptor 7 regulates pancreatic carcinogenesis in mice and humans. J. Clin. Invest. 2012;122 (11):4118-29. doi: 10.1172/JCI63606. PubMed PMID:23023703 PubMed Central PMC3484447.
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